In medicine several nucleoside derivatives and analogous, that is compounds having a structure similar to nucleosides but differing from nucleosides for a specific component such as for example one or more atoms, functional groups or sub-structures, are used as antiviral or antitumor agents. The high capability of these nucleoside derivatives and analogues to cross the cell membrane and to be converted into nucleoside within the cell makes such compounds very interesting for the research.
Specific examples of nucleoside analogous of pharmacological interest are azacytidine, decitabine, chlofarabine, cladribine, mizoribine.
Particularly azacytidine and decitabine are compounds of high interest in chemotherapy and in the treatment of diseases such as myelodysplasic syndrome.
Nucleosides and analogues thereof are typically synthetized by coupling an optionally protected purine or pyrimidine base, a derivative or an analogue thereof, with a ribose or deoxyribose derivative having an electrophilic center at the anomeric carbon.
A known example pyrimidine base analogue is 5-azacytosine.
Three types of synthesis of nucleosides, derivatives and analogues thereof are practically known in the prior art:                fusion method, which consists in heating the base and the sugar protected as acetyl at 155° C.        metal salt method, which consists in reacting a metal salt of the base with a halogenated derivative of the protected sugar        Hilbert-Johnson or Vorbruggen reaction (J. Org. Chem., Vol. 39, No. 25, 1974, 3672-3674), which consists in reacting the silylated base with the protected sugar having an acetyl group on the anomeric hydroxyl group, in the presence of a Lewis acid.        
U.S. Pat. No. 3,817,980 (Vorbruggen) describes a process for preparing 5-azapyrimidin-nucleoside derivatives by reaction of 2,4-bis-O-alkyl and 2,4-bis-O-silyl 5-azapyrimidine derivatives with a protected sugar derivative in the presence of a Lewis acid such as for example SnCl4, TiCl4, ZnCl2, BF3OEt2. The resultant azapyrimidin-nucleosides can be converted into the corresponding free nucleosides by simple saponification.
The process described by Vorbruggen shows some drawbacks due to the use of metal Lewis acids, particularly SnCl4, for the 5-azacytidine synthesis:                the nucleosides obtained by the coupling reaction contain a high amount of metals, particularly tin, difficult to remove;        during the aqueous work-up of the coupling reaction emulsions and colloids are formed slowing the phase separation. Then 5-azacytidine, which is unstable in water, remains for a long time in contact with an aqueous solution giving degradation products.        
For the above reasons, the process described by Vorbruggen is not suitable for the large-scale production of 5-azacytidine.